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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1485831

Honokiol protects against diabetic retinal microvascular injury via sirtuin 3-mediated mitochondrial fusion

Provisionally accepted
Jiemei Shi Jiemei Shi 1,2Min Liu Min Liu 1,2*Jiajie Zhao Jiajie Zhao 1,2*Ye Tan Ye Tan 3*Chunhui Jiang Chunhui Jiang 1,2*
  • 1 Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, shanghai, China
  • 2 Key laboratory of Myopia and Related Eye Diseases, NHC, Shanghai, China
  • 3 Gongli Hospital of Shanghai Pudong New Area, Shanghai, China

The final, formatted version of the article will be published soon.

    Mitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action. The effect of HKL was evaluated in vascular injury in an in vivo type 2 diabetic (db/db) mouse model. In vitro, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined. The diabetic mice exhibited severe retinal vascular damage, including vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL reversed the retinal vascular leakage in the diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the in vivo and in vitro protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation. In conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.

    Keywords: Diabetic Retinopathy, Retinal microvascular endothelial cells, sirt3, honokiol, Mitochondria

    Received: 26 Aug 2024; Accepted: 11 Oct 2024.

    Copyright: © 2024 Shi, Liu, Zhao, Tan and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Min Liu, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, shanghai, China
    Jiajie Zhao, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, shanghai, China
    Ye Tan, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China
    Chunhui Jiang, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.